PKDCC encodes a secreted tyrosine kinase that plays critical roles in skeletal development and extracellular protein regulation. The protein functions as an extracellular kinase that phosphorylates secreted proteins and components in the secretory pathway, representing part of a novel class of kinases that operate outside the traditional intracellular environment 1. PKDCC is essential for normal chondrogenesis and skeletal development, with particular importance in longitudinal bone growth through regulation of chondrocyte differentiation 2. The kinase mediates phosphorylation of matrix metalloproteinases and other extracellular substrates, influencing tissue patterning during organogenesis 1. Biallelic pathogenic variants in PKDCC cause rhizomelic limb shortening with dysmorphic features, a rare autosomal recessive skeletal dysplasia characterized by shortened proximal limbs, micrognathia, and hypertelorism 234. The condition shows predominantly upper limb involvement with delayed bone mineralization and altered chondrocyte proliferation 3. PKDCC variants also contribute to normal facial morphological variation and orofacial clefting risk through regulation of chondrogenesis 5. Additionally, PKDCC has been implicated in liver homeostasis, where it prevents perivascular fibrosis and inflammation through modulation of the hepatocyte secretome 6.